Invasive Breast Carcinoma with a DCIS-like Growth Pattern: Clinicopathological Features and Diagnostic Pitfalls

Invasive Breast Carcinoma with a DCIS-like Growth Pattern: Clinicopathological Features and Diagnostic Pitfalls | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Invasive Breast Carcinoma with a DCIS-like Growth Pattern: Clinicopathological Features and Diagnostic Pitfalls Xiaoyan Xu, YaoZhong Zhang, Huijuan Fang, Chuan Li, Xianwei Xu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8084081/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Ductal carcinoma in situ(DCIS)-like invasive carcinoma is a rare variant of expansile invasive breast cancer that is frequently misdiagnosed as ductal carcinoma in situ. However, some patients develop lymph node metastases exhibiting DCIS-like features, and there is limited literature documenting its clinicopathological characteristics.To characterize the clinicopathological features, immunophenotype, and diagnostic pitfalls of breast invasive carcinoma with a DCIS-like growth pattern (DCIS-like invasive carcinoma), a retrospective review of 319 breast carcinomas (January 2021–September 2025) identified 11 cases of DCIS-like invasive carcinoma. Clinical, histopathological, and immunophenotypic features were evaluated, and interobserver concordance for myoepithelial and basement membrane markers was assessed by 12 pathologists. Three tumors represented pure DCIS-like invasive carcinoma, and eight were admixed with invasive carcinoma of no special type (IBC-NST). Growth patterns included cribriform (6/11), papillary (3/11), solid (4/11), and comedo (5/11) and micropapillary(1/11). All tumors lacked myoepithelial marker expression (CK5/6, p63, CK14, SMA, Calponin), with Collagen IV confirming basement membrane loss; CK5/6 and CK14 showed perfect diagnostic reliability (κ = 1.00). Four patients developed axillary lymph node metastases in which the metastatic foci paradoxically retained DCIS-like morphology, directly confirming their invasive nature.Hormone receptor positivity was observed in 7/11 tumors, HER2 overexpression in 2/11, and the Ki-67 index ranged from 5–90%. With a mean follow-up of 13 months (range, 2–51 months), no local recurrence or distant metastasis was documented in 10 patients, DCIS-like structure was identified in cervical lymph node metastasis in one patient at 51 months postoperatively. DCIS-like invasive carcinoma is a rare and underrecognized entity that closely mimics DCIS and poses significant diagnostic challenges. The presence of lymph node metastases with DCIS-like morphology underscores its invasive potential. Accurate recognition requires careful morphological assessment in combination with multiple myoepithelial markers to avoid misdiagnosis and inappropriate clinical management. Invasive breast carcinoma of no special type (IBC-NST) Ductal carcinoma in situ (DCIS)-like growth diagnostic pitfall Myoepithelial cell loss Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Invasive carcinoma of the breast with a ductal carcinoma in situ (DCIS)-like growth pattern (DCIS-like invasive carcinoma) is a rare entity that poses substantial diagnostic challenges and is not yet recognized in the World Health Organization (WHO) Classification of Breast Tumors. Morphologically, it exhibits expansile DCIS-like structures-solid, papillary, cribriform, or comedo types-within invasive lesions, and even metastatic foci may paradoxically retain these in situ-like features [ 1 ]. The defining pathological hallmark is the complete absence of peripheral myoepithelial cells, a feature often overlooked, leading to misclassification as DCIS or encapsulated papillary carcinoma. Although sporadic case reports have described this pattern [ 2 – 4 ], consensus regarding its clinicopathological features, immunophenotypic profile, and diagnostic criteria remains lacking. The present study analyzed eleven cases of DCIS-like invasive carcinoma, with particular attention to morphological and immunohistochemical features and the diagnostic performance of myoepithelial and basement membrane markers. Importantly, a DCIS-like morphology was observed in four axillary and one cervical lymph node metastases, providing direct evidence of the invasive nature of this tumor type. Our findings highlight key diagnostic pitfalls and propose a diagnostic approach to facilitate accurate recognition, with implications for future updates to the WHO classification. Materials and Methods 1.1 Case selection A retrospective review of 319 archived breast carcinoma cases diagnosed at Zhengzhou People’s Hospital between January 2021 and September 2025 identified eleven tumors with a ductal carcinoma in situ (DCIS)–like growth pattern. Clinical data were retrieved for all cases. Inclusion criteria were: (i) histological evidence of DCIS-like expansile growth; (ii) immunohistochemical absence of myoepithelial markers (all tested markers negative); and (iii) loss of basement membrane integrity, indicated by disrupted Collagen IV staining. Histological grading of invasive carcinoma of no special type (IBC-NST) followed the Nottingham Histological Grading System. Follow-up data were collected via telephone through November 2025. This study was approved by the Ethics Committee of Zhengzhou People’s Hospital, with informed consent waived owing to its retrospective design. 1.2 Histology, immunohistochemistry, and FISH Specimens were fixed in 10% neutral buffered formalin, paraffin-embedded, and sectioned at 3–5 µm. Sections were stained with hematoxylin–eosin (H&E) and subjected to immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) when indicated. Primary antibodies included ER, PR, HER2, CK5/6, CK14, Calponin, p63, Collagen IV, Syn, CgA, CD56 and Ki-67 (Fuzhou Maixin Biotechnology, China). IHC was performed on an automated stainer (Dako, USA) using the streptavidin–peroxidase method, with appropriate positive and negative controls. ER, PR, HER2, and Ki-67 were independently assessed by two board-certified pathologists at the attending level or above. Myoepithelial and basement membrane markers were reviewed by 12 pathologists. Final consensus was reached by double-blind review from two senior breast specialists (> 10 years of experience), with discrepancies resolved through multidisciplinary team (MDT) discussion. Diagnostic performance of myoepithelial and basement membrane markers was evaluated based on interobserver concordance. 1.3 Interpretation of ER, PR, and HER2 ER and PR status were scored according to the 2020 ASCO/CAP guidelines [ 5 ]. Tumors with ≥ 10% nuclear staining were considered positive; 1%–<10% was designated low-positive, and < 1% was considered negative. For all positive cases, both the percentage and staining intensity were recorded. HER2 IHC was interpreted according to the 2023 ASCO/CAP guidelines [ 6 ]. IHC 0 was defined as no staining or ≤ 10% of tumor cells with incomplete or faint membrane staining; IHC 1 + as > 10% of tumor cells with incomplete and faint membrane staining; IHC 2 + as > 10% of tumor cells with weak to moderate, complete circumferential membrane staining, or ≤ 10% with strong complete staining; and IHC 3 + as > 10% of tumor cells with strong, complete, and uniform circumferential staining. Equivocal cases (IHC 2+) were further evaluated by HER2 fluorescence in situ hybridization (FISH), and amplification was determined according to the 2023 ASCO/CAP criteria. Results 2.1 Clinical Characteristics All eleven patients with DCIS-like invasive carcinoma were women, aged 43–75 years (mean, 56 years). Nine tumors occurred in the left breast and two in the right. Imaging (ultrasound or mammography) revealed hypoechoic or mixed-echo nodules with either circumscribed or irregular margins. By BI-RADS classification, four cases were category 3 and seven were category 4. Maximum tumor diameter ranged from 1.5 to 5.0 cm. All lesions presented as solitary solid nodules without fibrous capsules (Table 1 ). Table 1 Clinicopathological characteristics of 11 cases of DCIS-like invasive carcinoma. Case Age Location Tumor size BI-RADS (Ultrasound/Mammography) Surgical procedure Lymph nodes Treatment Prognosis 1 64 left 1.5x1.0x1.0cm 4 MRM 0/22 Endocrine therapy 24 months, no recurrence or metastasis 2 57 left 5.0x4.0x1.0cm 4 Breast-Conserving Surgery with SLNB 0/1 Endocrine therapy 24 months, no recurrence and metastasis 3 75 right 1.5x1.2x1.0cm 3 Simple Mastectomy with ALND 2/13 HER2-Targeted therapy plus Endocrine Therapy 16 months, no recurrence or metastasis 4 43 left 2.0×2.0×1.5cm 4 Breast-Conserving Surgery with SLNB 0/5 Endocrine therapy plus radiotherapy 4 months, no recurrence or metastasis 5 49 left 2.0×1.5×1.0cm 3 Simple Mastectomy with ALND 0/23 Chemotherapy and HER2-Targeted Therapy 10 months, no recurrence or metastasis 6 53 left 4.5×4.0×2.0cm 3 Breast-Conserving Surgery with SLNB 0/5 Chemotherapy 4 months, no recurrence or metastasis 7 44 left 4.5×4.0×3.2cm 3 MRM 3/25 Chemotherapy 6 months, no recurrence or metastasis 8 60 left 2.7×2.2×1.5cm 4 Breast-Conserving Surgery with ALND 4/24 Endocrine therapy 2 months, no recurrence or metastasis 9 46 right 2.0×2.0×1.5cm 4 Breast-Conserving Surgery with ALND 3/21 Endocrine therapy 2 months, no recurrence or metastasis 10 68 left 5.0×3.0×1.5cm 4 Breast-Conserving Surgery with SLNB 0/6 Endocrine therapy 2 months, no recurrence or metastasis 11 58 left 2.5×1.5×1.3cm 4 MRM 0/31 Chemotherapy 51months,cervical lymph node metastasis ALND:Axillary Lymph Node Dissection;MRM:Modified Radical Mastectomy ; SLNB:Sentinel Lymph Node Biopsy 2.2 Histological features Microscopically, tumors exhibited expansile, DCIS-like infiltration with scant stroma, smooth contours, and sharp demarcation from adjacent tissue. Peritumoral retraction spaces were occasionally present. Growth patterns included cribriform (6/11, Fig. 1 A), papillary (3/11, Fig. 1 B), solid (4/11, Fig. 1 C), comedo (5/11, Fig. 1 D),and Micropapillary(1/11, Fig. 1 E) often coexisting within the same tumor. Prominent lymphocytic infiltration was observed in comedo-type lesions (Case 5). eight cases (Cases 3, 4, 6, 7, 8, 9,10,11) contained both DCIS-like invasive carcinoma and invasive carcinoma of no special type (IBC-NST) (Fig. 1 F), graded II or III. Conventional DCIS was also present in Cases 3, 4,9,10 and 11. In four cases (Cases 3, 7, 8 and 9), axillary lymph node metastases displayed DCIS-like cribriform structures with smooth contours, closely resembling the primary tumor (Fig. 2 A and B). One case presented with vascular tumor thrombus resembling DCIS(Case 8, Fig. 2 C).A patient presented with cervical lymph node metastasis 51 months after surgery, in which a comedo-type growth pattern was observed in the metastatic lesion (Case 11, Fig. 2 D). Regarding nuclear grade of DCIS-like Growth Pattern, two tumors were low grade, two were low-to-intermediate, two was intermediate grade and five were high grade (Table 2 ). A: Cribriform growth pattern (Case 4, H&E, ×100);B:Papillary growth pattern (Case 4, H&E, ×100) ;C: Solid growth pattern (Case 3, H&E, ×100) ;D: Comedo-type growth pattern (Case 5, H&E, ×100) ;E: Micropapillary growth pattern (Case 9, H&E, ×100);F: DCIS-like invasive carcinoma coexisting with invasive carcinoma of no special type (Case 4, H&E, ×40) ; A: A loose cribriform pattern in anxillary lymph node metastases (Case 9, H&E, ×200);B: A dense cribriform pattern in axillary lymph node metastases (Case 3, H&E, × 200); C: Tumor emboli with a DCIS-like pattern were identified within vascular spaces (Case 8, H&E, ×200);D:Comedo pattern in cervical lymph node metastases (Case 11, H&E, ×200) Table 2 Histopathological and Immunophenotypic Features of 11 Cases of DCIS-like Invasive Carcinoma Case DCIS-like Growth Pattern Grade of IBC-NST DCIS-like Nuclear Grade ER/PR/Her2 Her2 FISH Ki67 Index Molecular Subtype Original Pathological Diagnosis 1 Papillary/Cribriform / Low grade 90% strongly positive/90% strongly positive/(2+) - 5% LuminalA encapsulated papillary carcinoma with DCIS 2 Papillary/Cribriform / Low grade 70%moderate-to-strongly positive/60%moderate-to-strongly positive/(2+) - 5% LuminalA encapsulated papillary carcinoma with DCIS 3 Solid/Cribriform II grade High grade 90%strongly positive+/70%strongly positive+/(3+) Not amplified 50% LuminalB(Her2 positive) IBC-NST with DCIS 4 Papillary/Cribriform II grade Low- to intermediate-grade 80%strongly positive/80%strongly positive/(2+) - 15% LuminalA IBC-NST with DCIS 5 Comedo / High grade Negative/Negative/(3+) Not amplified 90% Her2 -overexpressing IBC-NST 6 Solid/Comedo III grade High grade -/-/(0) - 80% Triple-negative type IBC-NST 7 Solid/Comedo III grade High grade -/-/(0) - 90% Triple-negative type IBC-NST 8 Cribriform III grade Intermediate-grade 90%strongly positive/20%strongly positive/(1+) 50% LuminalB IBC-NST 9 Cribriform/micropapillary II grade Low- to intermediate-grade 90%strongly positive/90%strongly positive/(1+) 20% LuminalB IBC-NST with DCIS 10 Solid/Comedo II grade Intermediate-grade 90%moderately positive/90%moderately positive/(1+) 10% LuminalA IBC-NST with DCIS 11 Comedo III grade High grade -/-/(0) 90% Triple-negative type IBC-NST with DCIS IBC-NST = invasive carcinoma of no special type 2.3 Immunohistochemical findings All tumors (11/11) lacked expression of myoepithelial markers (CK5/6, p63, CK14, SMA, Calponin), and Collagen IV confirmed loss of basement membrane (Figs. 3 A–F, 4 A–F). By contrast, DCIS components in Cases 3,4,9,10 and 11 showed intact myoepithelial marker expression and preserved basement membrane (Fig. 5 A–F). Seven tumors were ER-positive (70–90%) and seven were PR-positive (60–90%). HER2 status was 0 in three cases, 1 + in three cases, 2 + in three cases, and 3 + in two cases (Fig. 6 A–F, Table 2 ). All HER2 2 + tumors were non-amplified by FISH. None expressed neuroendocrine markers (Syn, CgA, CD56). Ki-67 index ranged from 5% to 90%. In Cases 3, 4, 6, 7, 9,10 and 11, IBC-NST components exhibited the same ER/PR/HER2 profiles as the DCIS-like invasive component. A:CK5/6 demonstrating loss of myoepithelial cells ;B: CK14 demonstrating loss of myoepithelial cells;C: p63 demonstrating loss of myoepithelial cells;D: Calponin demonstrating loss of myoepithelial cells ;E:SMA demonstrating loss of myoepithelial cells;F: Collagen IV showing absent basement membrane A: CK5/6 demonstrating loss of myoepithelial cells;B:CK14 demonstrating loss of myoepithelial cells;C:p63 demonstrating loss of myoepithelial cells; D:Calponin demonstrating loss of myoepithelial cells;E:SMA demonstrating loss of myoepithelial cells; F: Collagen IV showing absent basement membrane A:CK5/6 demonstrating intact myoepithelial layer(Case3); B: CK14 demonstrating intact myoepithelial layer(Case3); C: p63 demonstrating intact myoepithelial layer(Case3); D: Calponin cytoplasmic staining forming intraluminal protrusions(Case3); E:SMA cytoplasmic staining forming intraluminal protrusions(Case3); F:Collagen IV demonstrating continuous basement membrane(Case3) A: ER 90% strongly positive;B:PR 90% strongly positive; C: HER2 (2+); D:ER negative; E: PR negative; F:HER2 (3+) (A-C: Case 4; D-F: Case 5; IHC, ×100) 2.4 Inter-Observer Concordance Analysis of Myoepithelial Markers and Collagen IV Comparative analysis of several myoepithelial markers revealed that SMA and Calponin staining exhibited cytoplasmic localization in ductal carcinoma in situ (DCIS), forming intraluminal protrusions, with positive cells positioned internal to the basement membrane. However, frequent cross-reactivity with stromal myofibroblasts and vascular pericytes introduced significant diagnostic interference. Collagen IV staining demonstrated poor reliability due to background non-specific staining and positivity in vascular basement membranes. In contrast, CK5/6, CK14, and p63 exhibited clean background staining with minimal non-specific reactivity, allowing for consistent and reliable interpretation (Figs. 7 A-D). Twelve pathologists independently evaluated myoepithelial markers (CK5/6, CK14, p63, SMA, Calponin) and basement membrane marker Collagen IV in 11 cases of in situ-like invasive carcinoma. CK5/6 and CK14 demonstrated perfect diagnostic performance (false-positive rate = 0%, κ = 1.00), whereas Collagen IV showed poor reliability (false-positive rate = 38.6%, κ = 0.23) and should be used cautiously with supplementary markers. Pathologists' interpretations, detailed performance metrics, and sources of discordance are summarized in Tables 3 and 4 . A: Calponin staining in in situ-like invasive carcinoma shows loss of myoepithelial cells. Tumor-surrounding stromal fibroblasts and pericytes are positive;B: SMA staining in in situ-like invasive carcinoma shows loss of myoepithelial cells. Tumor-surrounding stromal fibroblasts and pericytes are positive;C: Calponin staining in ductal carcinoma in situ reveals intraluminal protrusions due to cytoplasmic staining;D: SMA staining in ductal carcinoma in situ reveals intraluminal protrusions due to cytoplasmic staining. Table 3 Interobserver Concordance in Myoepithelial/Basement Membrane Marker Interpretation for DCIS-like Invasive Carcinoma Among 12 Pathologists (11 Cases) Case Immunohistochemical markers (Number of pathologists interpreting loss of expression / Total pathologists) CK5/6 CK14 P63 SMA Calponin Collagen IV 1 12/12 12/12 10/12 8/12 8/12 1/12 2 12/12 12/12 12/12 7/12 6/12 0/12 3 12/12 12/12 12/12 9/12 8/12 2/12 4 12/12 12/12 12/12 8/12 8/12 1/12 5 12/12 12/12 12/12 12/12 12/12 12/12 6 12/12 12/12 12/12 12/12 12/12 12/12 7 12/12 12/12 12/12 12/12 12/12 12/12 8 12/12 12/12 12/12 12/12 7/12 10/12 9 12/12 12/12 12/12 12/12 12/12 8/12 10 12/12 12/12 12/12 12/12 8/12 9/12 11 12/12 12/12 12/12 12/12 12/12 8/12 Table 4 Diagnostic Performance of Myoepithelial/Basement Membrane Markers in DCIS-like Invasive Carcinoma (n = 132 evaluations;11 cases × 12 pathologists) Maker False Positive Rate(%) Specificity(%) (95%CI) Kappa vs,Gold Standard(95%CI) Agreement Level Major Interpretive Discrepancies CK5/6 0(0.0-2.8) 100.0(97.2–100) 1.0(1.00–1.00) Almost perfect None CK14 0(0.0-2.8) 100.0(97.2–100) 1.0(1.00–1.00) Almost perfect None P63 1.5(0.2–5.4) 98.5(94.6–99.8) 0.91(0.82-1.00) Substantial Weak nuclear staining in some luminal epithelial cells SMA 15.9(9.9–23.8) 84.1(76.2–90.1) 0.68(0.56–0.80) Moderate Interference from pericytes and myofibroblasts Calponin 18.2(11.8–26.4) 81.8(73.6–88.2) 0.64(0.52–0.76) Moderate Interference from pericytes and myofibroblasts Collagen IV 38.6%(30.2–47.7) 61.4(52.3–69.8) 0.23(0.10–0.36) Poor Non-specific staining, interference from vascular basement membranes Notes: Kappa grading based on Landis & Koch criteria 2.5 Correlation Between Molecular Subtypes and Growth Patterns Four cases (n = 4/11) with predominantly cribriform/papillary or solid/comedo growth patterns were Luminal A type(Case1, 2, 4 and 10). Three cases (n = 3/11) were of the Luminal B subtype, including one with a solid/cribriform growth pattern (HER2-overexpressing, Case 3), one with a cribriform growth pattern (Case 8), and one with a cribriform/micropapillary growth pattern(Case 9).One case (n = 1/11) with predominantly comedo-type growth was HER2-overexpressing(Case 5). Three cases (n = 3/11) showing predominantly solid/comedo-type growth were triple-negative(Case6,7 and 11). (Table 2 ). 2.6 Pathological Diagnostic Concordance Two pure DCIS-like invasive carcinoma (Cases 1 and 2) with papillary/cribriform patterns were initially misdiagnosed as encapsulated papillary carcinoma with concurrent DCIS. Five cases (5/11, Case 3,4,9,10 and 11), which coexisted with NST and DCIS, were initially misinterpreted as DCIS due to their DCIS-like growth pattern. One case (1/11, Case 5) of pure comedo-type invasive carcinoma was correctly diagnosed as IBC-NST on routine immunohistochemistry due to the absence of myoepithelial cells. Three cases (3/11, Case 6, 7 and 8) with cribriform, solid or comedo patterns, accompanied by IBC-NST, were diagnosed as IBC-NST, with the DCIS-like invasive component being overlooked. (Table 2 ). 2.7 Treatment and Outcomes Among the eleven patients, modified radical mastectomy(MRM) was performed in Cases 1/7/11, breast-conserving surgery with sentinel lymph node biopsy (SLNB) in Cases 2/4/6/10, breast-conserving Surgery with axillary lymph node dissection (ALND) in Cases 8 and 9, and simple mastectomy with ALND in Cases 3 and 5. Axillary lymph node metastases were identified in Cases 3/7/8/9. Adjuvant therapy included endocrine therapy (Cases 1, 2,8,9 and 10), anti-HER2 + endocrine therapy (Case 3), endocrine therapy + radiotherapy (Case 4), chemotherapy + anti-HER2 (Case 5), and chemotherapy (Cases 6, 7,11). After a mean follow-up of 13 months (range 2–51 months), 10 patients remained disease-free and maintained good performance status, one patient presented with cervical lymph node metastasis 51 months after surgery, in which a comedo-type growth pattern was observed in the metastatic lesion (Case11). (Table 1 ). Discussion This study highlights the clinicopathological spectrum of breast invasive carcinoma with a DCIS-like growth pattern, an underrecognized entity that poses major diagnostic challenges. Importantly, we report axillary and cercical lymph node metastases retaining DCIS-like morphology, providing direct evidence that this pattern represents an invasive carcinoma rather than an in situ lesion. Expansile invasion, though rarely addressed in the breast literature, can mimic DCIS due to its rounded nests, papillary, cribriform, or comedo-type structures with smooth contours and minimal stromal reaction. These features often lead to misclassification as DCIS, solid papillary carcinoma, or encapsulated papillary carcinoma. In our series, two cases were initially diagnosed as encapsulated papillary carcinoma with DCIS, DCIS-like invasive carcinoma was misclassified as DCIS in cases of IBC-NST with DCIS, while in other cases of IBC-NST the presence of DCIS-like invasive carcinoma was overlooked. Careful recognition of the absence of myoepithelial cells is essential to avoid misdiagnosis. Earlier reports have described similar tumors mimicking comedo-type or micropapillary DCIS [ 1 – 4 , 7 – 9 ]. Zhang et al. [ 9 ] emphasized the diagnostic value of multiple myoepithelial markers, while Wynveen et al. [ 10 ] demonstrated that collagen IV positivity does not preclude invasion, as re-formation of basement membrane may occur after tumor penetration. Our findings support these observations and further demonstrate that diagnostic accuracy is maximized by using CK5/6 and CK14, which achieved perfect concordance among pathologists in this study. In contrast to previous studies suggesting enrichment for ER-negative phenotypes [ 11 ], our cohort displayed molecular heterogeneity: Luminal A (n = 4), Luminal B (n = 3), HER2 overexpression (n = 1), and triple-negative (n = 3). Nuclear grades ranged from low to high, and comedo-type tumors were often associated with lymphocytic infiltration, suggesting that the tumor microenvironment may influence invasiveness. DCIS-like invasive carcinoma must be carefully distinguished from several morphologically overlapping entities. Conventional DCIS typically retains a continuous layer of myoepithelial cells, which can be confirmed using markers such as CK5/6, CK14 and p63. In contrast, DCIS-like invasive carcinomas lack myoepithelial cells and may exhibit subtle stromal reaction, necessitating immunohistochemical confirmation across multiple markers.Encapsulated papillary carcinoma (EPC) often presents as a well-circumscribed lesion with absent peripheral myoepithelial cells but typically displays low-grade cytology and rarely metastasizes, unlike the cases presented in our study. Solid papillary carcinoma (SPC) may also be mistaken for DCIS-like invasion but frequently expresses neuroendocrine markers (e.g., synaptophysin, chromogranin) and contains delicate fibrovascular cores. Integration of morphologic assessment with immunohistochemical profiling is essential to avoid diagnostic errors and ensure appropriate clinical management. The presence of DCIS-like morphology in lymph node metastases, both in our series and in prior reports [ 12 – 15 ], underscores the invasive nature of these tumors despite their deceptively in situ-like appearance. Misinterpretation may lead to inappropriate treatment strategies. For equivocal DCIS cases, immunohistochemical confirmation of absent myoepithelial markers should be mandatory. Awareness of this entity and its key differential diagnoses—including DCIS, EPC, and SPC—is essential, and accurate classification requires a panel-based approach combining myoepithelial and neuroendocrine markers with morphological features. This study is limited by its small sample size, lack of genomic profiling, and short follow-up period. Larger multi-center studies integrating molecular and spatial-omics analyses are warranted to further define the biology of DCIS-like invasive carcinoma and its optimal management. Abbreviations DCIS Ductal carcinoma in situ IBC-NST Invasive breast carcinoma of no special type SPC Solid papillary carcinoma EPC Encapsulated papillary carcinoma ER Estrogen receptor PR Progesterone receptor HER2 Human Epidermal growth factor Receptor 2 IHC World Health Organization CgA Chromogranin A Syn Synaptophysin FISH Fluorescence in situ hybridization Declarations Acknowledgements We thank the study participants for making this study possible. Authors’ contributions Xiaoyan Xu was responsible for manuscript writing, figure preparation, and data analysis. Yaozhong Zhang participated in manuscript revision. Huijuan Fang and Chuan Li conducted case collection. Xianwei Xu performed the immunohistochemical staining. Huang Jiang and Liu Yang contributed to the study design and manuscript revision. Funding This study was supported by Zhengzhou City Technological Innovation Progect(2025YLZDJH311) Data availability All data are included in the manuscript. Ethics approval and consent to participate All procedures carried out in studies involving human participants complied with the ethical standards of the Research Committee of Zhengzhou People’s Hospital and the 1964 Declaration of Helsinki and subsequent amendments or similar ethical standards. The study was approved by the Bioethics Committee of Zhengzhou People’s Hospital(2025-KY-009901). All subjects gave informed consent to participate in the study. All methods were performed in accordance with relevant guidelines and regulations. Consent to Publish declaration Not applicable Competing interests The authors declare no competing interests. References Cowen PN, Bates C. The significance of intraduct appearances in breast cancer. Clin Oncol. 1984;10(1):67–72. Salisbury T, Rendi M, Bhalli R, et al. DCIS-like invasive carcinoma of the breast with tumour-associated microvasculature mimicking myoepithelium: a diagnostic pitfall. Histopathology. 2025;87(2):246–57. Ji J, Shi M, Duan F, et al. A case of invasive ductal carcinoma with in situ pattern of the breast. Chin Med Case Rep. 2023;5(1):e00232. Mohan N, Black JO, Schwartz MR, Zhai QJ. Invasive ductal carcinoma with in situ pattern: how to avoid this diagnostic pitfall? Am J Transl Res. 2016;8(8):3337–41. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38(12):1346–66. Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-CAP guideline update. J Clin Oncol. 2023;41(22):3867–72. Pervez S, Khan H. Infiltrating ductal carcinoma of the breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type): a case series. J Med Case Rep. 2007;1:83. Tijani S, Sharma K, Yuen H, Shaaban A. Metastatic ductal carcinoma in situ-like lobular carcinoma in a lymph node: a case report and review of the literature. Int J Surg Pathol. 2020;28(4):436–9. Zhang X, Ding H. Morphological changes of expansile invasion in mammary tumors and their significance in pathological diagnosis. Zhonghua Bing Li Xue Za Zhi. 2014;43(5):291–5. Wynveen CA, Nehhozina T, Akram M, et al. Intracystic papillary carcinoma of the breast: an in situ or invasive tumor? Results of immunohistochemical analysis and clinical follow-up. Am J Surg Pathol. 2011;35(1):1–14. Barsky SH, Doberneck SA, Sternlicht MD, Grossman DA, Love SM. Revertant DCIS in human axillary breast carcinoma metastases. J Pathol. 1997;183(2):188–94. Cserni G. Revertant mammary solid papillary carcinoma in lymph node metastasis. Pathol Oncol Res. 2002;8(1):74–7. Coyne J. Metastatic mammary carcinoma with DCIS-like morphology: a report of two cases. Int J Surg Pathol. 2012;20:485–7. Kordek R. Ductal carcinoma in situ-like structures in metastatic breast carcinoma. Pathol Res Pract. 2005;200(11–12):831–4. Liu Y, Huang H, Zhang M, et al. Clinicopathological analysis of metastatic breast cancer with ductal carcinoma in situ-like growth pattern. Zhonghua Bing Li Xue Za Zhi. 2018;47(10):784–5. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8084081","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":559608990,"identity":"4976fc64-893c-4880-9e90-6ba4468c9bfd","order_by":0,"name":"Xiaoyan Xu","email":"","orcid":"","institution":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Xu","suffix":""},{"id":559608991,"identity":"3e5f04e6-f104-440d-bc97-0c688cf8870f","order_by":1,"name":"YaoZhong Zhang","email":"","orcid":"","institution":"Fox Chase Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"YaoZhong","middleName":"","lastName":"Zhang","suffix":""},{"id":559608992,"identity":"4fbcda2a-4e5f-4bfc-ab22-0bbde43d3260","order_by":2,"name":"Huijuan Fang","email":"","orcid":"","institution":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Huijuan","middleName":"","lastName":"Fang","suffix":""},{"id":559608993,"identity":"c671a551-2ea7-4f1e-aa8f-5aaff0913cff","order_by":3,"name":"Chuan Li","email":"","orcid":"","institution":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Chuan","middleName":"","lastName":"Li","suffix":""},{"id":559608994,"identity":"70027401-5b41-4870-a415-e0243492d85d","order_by":4,"name":"Xianwei Xu","email":"","orcid":"","institution":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Xianwei","middleName":"","lastName":"Xu","suffix":""},{"id":559608995,"identity":"33dab12a-122e-4e40-bfb0-6b994de49632","order_by":5,"name":"Huang Jiang","email":"","orcid":"","institution":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Huang","middleName":"","lastName":"Jiang","suffix":""},{"id":559608996,"identity":"8fbb8985-5c14-42d3-935f-da09af176f18","order_by":6,"name":"Liu Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYBACNvbmA4d//mGT4ydaCx/PscTHjA18xpINxGqRk8gxNmZskEvccIBohzGkpUkX7jAzNj6evIHhR8U2YrQcPiY980yanNmZZwWMPWduE6GFsS1NgoftmLHZjRwDZsY2YrQw85gBtfxP3DyDaC1sPMbGvG1siRskiNbCw5b4cMYZNmMJoF8OEuUX+fmPDxz4UAGMyvbkjQ9+VBChBQkkGBwgST1YC6k6RsEoGAWjYIQAALvXPBKL/iEuAAAAAElFTkSuQmCC","orcid":"","institution":"Nanchang People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Liu","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-11-11 08:08:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8084081/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8084081/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98218025,"identity":"5052e80e-b48a-4370-a997-a88d6bb14fee","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":26364015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/3d7c5c6e6ed86aea42cba6cb.docx"},{"id":98217995,"identity":"37028afe-eee7-45d5-9516-355451ff09d0","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8730,"visible":true,"origin":"","legend":"","description":"","filename":"9a6fa30447774ee3997025e3d93f2d00.json","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/866769b834197a252870b932.json"},{"id":98432881,"identity":"9c6994d1-bef8-41c6-abda-3a321bef2c3e","added_by":"auto","created_at":"2025-12-17 16:50:05","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":91606,"visible":true,"origin":"","legend":"","description":"","filename":"9a6fa30447774ee3997025e3d93f2d001enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/25fc5de89d9d45c7c3b58e3a.xml"},{"id":98218008,"identity":"827dc5dd-c0e1-46bc-9ba9-b5bcdd2ffbf1","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1481397,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/8f4bf2aae54b8c2dd4228ae0.jpeg"},{"id":98218001,"identity":"a1f4416c-5a98-4143-9de2-634dd91deafb","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1485475,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/20d9a2040d0b4179cbd9ecf9.jpeg"},{"id":98218003,"identity":"d87a8eec-e489-4193-98e7-864c501ac9bc","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1308069,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage11.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/352991b4ca1e638adcdcf946.jpeg"},{"id":98433686,"identity":"d0c53c1f-7eeb-4ca8-bc68-c7734c6851be","added_by":"auto","created_at":"2025-12-17 16:51:02","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1294918,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage12.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/74e64b7fd92e6d4eea43c81c.jpeg"},{"id":98431856,"identity":"07ff6839-3550-4981-b85d-26942632dc1c","added_by":"auto","created_at":"2025-12-17 16:48:28","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1074746,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage13.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/7ba1aa42da02185b7b9e4425.jpeg"},{"id":98433867,"identity":"8e07201b-3eda-4227-ae8e-8a4576abd454","added_by":"auto","created_at":"2025-12-17 16:51:11","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1491736,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/6c182e188f916d1ad9bcf7c3.jpeg"},{"id":98218005,"identity":"fc41f338-fe81-4ab2-8f43-3892eb189101","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1354745,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/ad0b2cbf5b70c5a5a2b3b7ca.jpeg"},{"id":98218026,"identity":"aaa653a8-bf22-4551-abf4-cf9e96a91c3b","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"jpeg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1261512,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/8c08683218b8d7db84526af2.jpeg"},{"id":98431787,"identity":"e9506aa3-0f95-4fdc-b3fc-d912a8dcbf6c","added_by":"auto","created_at":"2025-12-17 16:48:22","extension":"jpeg","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1105613,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/000b7f950fe8be94f8fd2973.jpeg"},{"id":98432426,"identity":"8011345e-64b8-4cc8-9b61-9a8eae50b8a6","added_by":"auto","created_at":"2025-12-17 16:49:32","extension":"jpeg","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1173540,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/dd55d0466e40385e6d81f007.jpeg"},{"id":98433638,"identity":"c2b68cff-10d6-4f1d-b42b-04b9973ccdff","added_by":"auto","created_at":"2025-12-17 16:50:58","extension":"jpeg","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2515778,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/d96924155945e8b61fd4fceb.jpeg"},{"id":98218017,"identity":"9e5868cd-f091-43db-8460-7252d0c06498","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpeg","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1154195,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/6517859991e902940f98d0d4.jpeg"},{"id":98218012,"identity":"ce90d33e-2420-4e34-998b-f59e8c229827","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpeg","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1356641,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/c99775b3ba58bfa23f774e41.jpeg"},{"id":98431852,"identity":"9c23e7a7-5270-45cf-8d9d-6005d78a9c01","added_by":"auto","created_at":"2025-12-17 16:48:28","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":526696,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/922042c526857439584d6dd4.png"},{"id":98433661,"identity":"097e50c4-b7b4-4f79-9e0a-35cda84427c9","added_by":"auto","created_at":"2025-12-17 16:51:00","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":577862,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/55d7254085cc46664f5757ac.png"},{"id":98218020,"identity":"221148c2-e0c1-4636-8861-04afd7e34f07","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":400650,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/61955247160b31b3cea54458.png"},{"id":98218015,"identity":"52cb167d-f59f-4b28-bc24-7543c230d757","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":490262,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/05241f45abf6380d60247bd6.png"},{"id":98433719,"identity":"d4898987-066c-46fe-88f9-87378be0da96","added_by":"auto","created_at":"2025-12-17 16:51:04","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":370331,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage13.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/fe6f55d24b1aa8861e63a728.png"},{"id":98218024,"identity":"370de999-c8e3-44d0-b267-933507905cc6","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"png","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":518613,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/380acb8aa0ae54ed3fa18eb0.png"},{"id":98432283,"identity":"f481ed53-3080-4c65-866a-c62df733c71b","added_by":"auto","created_at":"2025-12-17 16:49:20","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":598887,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/742f6e662711c164cb9a8dd8.png"},{"id":98432439,"identity":"b2413617-1332-4905-a328-604e880dc21b","added_by":"auto","created_at":"2025-12-17 16:49:33","extension":"png","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":476638,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/69c4263d17d955bdec3b65db.png"},{"id":98432490,"identity":"9bf3b75a-ce13-49c9-8e58-851d5da48dd1","added_by":"auto","created_at":"2025-12-17 16:49:37","extension":"png","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":512988,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/27ee2b1fe70bfad9cda9acb7.png"},{"id":98218031,"identity":"171498a2-1715-436a-a3ab-f45b6f3b3482","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"png","order_by":25,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":354411,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/544fad22028e8079d02f936e.png"},{"id":98218028,"identity":"9068525a-7ec1-4669-9102-ced51af08663","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"png","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":818167,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/928aa2c2266ab879feeeb510.png"},{"id":98218022,"identity":"c5c17b46-14f2-4267-850f-275120257261","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"png","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":352004,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/815d1fbf897803de7dac4408.png"},{"id":98431851,"identity":"6cd862b8-b5b6-41b6-83ff-d04e0144bf82","added_by":"auto","created_at":"2025-12-17 16:48:28","extension":"png","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":490934,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/39b9dff34d9f85c484029543.png"},{"id":98218029,"identity":"6fdd4357-eb5f-4b4a-acbf-422a1086bde1","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"xml","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":88105,"visible":true,"origin":"","legend":"","description":"","filename":"9a6fa30447774ee3997025e3d93f2d001structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/0239a401ddf4c50c734d5ea7.xml"},{"id":98218033,"identity":"d747af40-f210-4048-9313-356fcbf38415","added_by":"auto","created_at":"2025-12-15 10:59:35","extension":"html","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":96896,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/e5b6f77b85c9b6b90a4c2c0b.html"},{"id":98217994,"identity":"4b1cafc3-1561-40fe-81e5-e034ee0672f9","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":246902,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathological Features of DCIS-like Invasive Carcinoma\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA: Cribriform growth pattern (Case 4, H\u0026amp;E, ×100);B:Papillary growth pattern (Case 4, H\u0026amp;E, ×100) ;C: Solid growth pattern (Case 3, H\u0026amp;E, ×100) ;D: Comedo-type growth pattern (Case 5, H\u0026amp;E, ×100) ;E: Micropapillary growth pattern (Case 9, H\u0026amp;E, ×100);F: DCIS-like invasive carcinoma coexisting with invasive carcinoma of no special type (Case 4, H\u0026amp;E, ×40) ;\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/0d596bf9cb3ee49d41498dbc.jpg"},{"id":98217999,"identity":"44223514-ac11-4abd-a334-32e2ce7be0da","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":285386,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDCIS-like pattern in lymph node metastases and vascular spaces\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA: A loose cribriform pattern in anxillary lymph node metastases (Case 9, H\u0026amp;E, ×200);B：A dense cribriform pattern in axillary lymph node metastases (Case 3, H\u0026amp;E, × 200); C: Tumor emboli with a DCIS-like pattern were identified within vascular spaces (Case 8, H\u0026amp;E, ×200)；D:Comedo pattern in cervical lymph node metastases (Case 11, H\u0026amp;E, ×200)\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/d429a4478a229203285f2d6f.jpg"},{"id":98217996,"identity":"4545eb78-a79a-4528-a4dc-db3ca4998dcb","added_by":"auto","created_at":"2025-12-15 10:59:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":159699,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMyoepithelial/Basement Membrane Markers in Low-Nuclear-Grade DCIS-like Invasive Carcinoma (Case 4, IHC, ×100)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA:CK5/6 demonstrating loss of myoepithelial cells ;B: CK14 demonstrating loss of myoepithelial cells;C: p63 demonstrating loss of myoepithelial cells;D: Calponin demonstrating loss of myoepithelial cells ;E:SMA demonstrating loss of myoepithelial cells;F: Collagen IV showing absent basement membrane\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/dc57e88e3be2c86f04dfcb87.jpg"},{"id":98433772,"identity":"281f294d-6398-4508-b9cf-a6dab106ef5d","added_by":"auto","created_at":"2025-12-17 16:51:06","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":185593,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMyoepithelial/Basement Membrane Markers in High-Nuclear-Grade DCIS-like Invasive Carcinoma (Case 3, IHC, ×100)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA: CK5/6 demonstrating loss of myoepithelial cells;B:CK14 demonstrating loss of myoepithelial cells;C:p63 demonstrating loss of myoepithelial cells; D:Calponin demonstrating loss of myoepithelial cells;E:SMA demonstrating loss of myoepithelial cells; F: Collagen IV showing absent basement membrane\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/dc559eb38b9e02740c52b780.jpg"},{"id":98433658,"identity":"0531dcae-a294-413a-9e1e-dfea93bb166c","added_by":"auto","created_at":"2025-12-17 16:51:00","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":197884,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMyoepithelial/Basement Membrane Markers in DCIS(Case 3, IHC, ×100)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA:CK5/6 demonstrating intact myoepithelial layer(Case3); B: CK14 demonstrating intact myoepithelial layer(Case3); C: p63 demonstrating intact myoepithelial layer(Case3); D: Calponin cytoplasmic staining forming intraluminal protrusions(Case3); E:SMA cytoplasmic staining forming intraluminal protrusions(Case3); F:Collagen IV demonstrating continuous basement membrane(Case3)\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/9348dcaf5975c3bce3b60284.jpg"},{"id":98433606,"identity":"b9f8d89b-8fd8-4694-a27e-8f61ba58a695","added_by":"auto","created_at":"2025-12-17 16:50:56","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":207898,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHormone Receptor and HER2 Status in DCIS-like Invasive Carcinoma\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA: ER 90% strongly positive;B:PR 90% strongly positive; C: HER2 (2+); D:ER negative; E: PR negative; F:HER2 (3+)\u003c/p\u003e\n\u003cp\u003e(A-C: Case 4; D-F: Case 5; IHC, ×100)\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/b592cc814286d97a14543250.jpg"},{"id":98433609,"identity":"7b7c9872-84e9-4073-b0cb-ffaa06c6dd4f","added_by":"auto","created_at":"2025-12-17 16:50:56","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":206820,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Calponin and SMA Staining in In Situ-like Invasive Carcinoma and Ductal Carcinoma In Situ (Case 4, immunohistochemistry, 400× magnification)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA: Calponin staining in in situ-like invasive carcinoma shows loss of myoepithelial cells. Tumor-surrounding stromal fibroblasts and pericytes are positive;B: SMA staining in in situ-like invasive carcinoma shows loss of myoepithelial cells. Tumor-surrounding stromal fibroblasts and pericytes are positive;C: Calponin staining in ductal carcinoma in situ reveals intraluminal protrusions due to cytoplasmic staining;D: SMA staining in ductal carcinoma in situ reveals intraluminal protrusions due to cytoplasmic staining.\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/12da53807a8e720c6913036e.jpg"},{"id":99789990,"identity":"5ea682b3-83b7-47c0-822f-4a950166f635","added_by":"auto","created_at":"2026-01-08 12:51:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2783414,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8084081/v1/36a2e196-0b76-4b51-b073-91a6d7724071.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Invasive Breast Carcinoma with a DCIS-like Growth Pattern: Clinicopathological Features and Diagnostic Pitfalls","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInvasive carcinoma of the breast with a ductal carcinoma in situ (DCIS)-like growth pattern (DCIS-like invasive carcinoma) is a rare entity that poses substantial diagnostic challenges and is not yet recognized in the World Health Organization (WHO) Classification of Breast Tumors. Morphologically, it exhibits expansile DCIS-like structures-solid, papillary, cribriform, or comedo types-within invasive lesions, and even metastatic foci may paradoxically retain these in situ-like features [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe defining pathological hallmark is the complete absence of peripheral myoepithelial cells, a feature often overlooked, leading to misclassification as DCIS or encapsulated papillary carcinoma. Although sporadic case reports have described this pattern [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], consensus regarding its clinicopathological features, immunophenotypic profile, and diagnostic criteria remains lacking.\u003c/p\u003e\u003cp\u003eThe present study analyzed eleven cases of DCIS-like invasive carcinoma, with particular attention to morphological and immunohistochemical features and the diagnostic performance of myoepithelial and basement membrane markers. Importantly, a DCIS-like morphology was observed in four axillary and one cervical lymph node metastases, providing direct evidence of the invasive nature of this tumor type. Our findings highlight key diagnostic pitfalls and propose a diagnostic approach to facilitate accurate recognition, with implications for future updates to the WHO classification.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e1.1 Case selection\u003c/h2\u003e\u003cp\u003eA retrospective review of 319 archived breast carcinoma cases diagnosed at Zhengzhou People\u0026rsquo;s Hospital between January 2021 and September 2025 identified eleven tumors with a ductal carcinoma in situ (DCIS)\u0026ndash;like growth pattern. Clinical data were retrieved for all cases. Inclusion criteria were: (i) histological evidence of DCIS-like expansile growth; (ii) immunohistochemical absence of myoepithelial markers (all tested markers negative); and (iii) loss of basement membrane integrity, indicated by disrupted Collagen IV staining. Histological grading of invasive carcinoma of no special type (IBC-NST) followed the Nottingham Histological Grading System. Follow-up data were collected via telephone through November 2025. This study was approved by the Ethics Committee of Zhengzhou People\u0026rsquo;s Hospital, with informed consent waived owing to its retrospective design.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e1.2 Histology, immunohistochemistry, and FISH\u003c/h2\u003e\u003cp\u003eSpecimens were fixed in 10% neutral buffered formalin, paraffin-embedded, and sectioned at 3\u0026ndash;5 \u0026micro;m. Sections were stained with hematoxylin\u0026ndash;eosin (H\u0026amp;E) and subjected to immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) when indicated. Primary antibodies included ER, PR, HER2, CK5/6, CK14, Calponin, p63, Collagen IV, Syn, CgA, CD56 and Ki-67 (Fuzhou Maixin Biotechnology, China). IHC was performed on an automated stainer (Dako, USA) using the streptavidin\u0026ndash;peroxidase method, with appropriate positive and negative controls.\u003c/p\u003e\u003cp\u003eER, PR, HER2, and Ki-67 were independently assessed by two board-certified pathologists at the attending level or above. Myoepithelial and basement membrane markers were reviewed by 12 pathologists. Final consensus was reached by double-blind review from two senior breast specialists (\u0026gt;\u0026thinsp;10 years of experience), with discrepancies resolved through multidisciplinary team (MDT) discussion. Diagnostic performance of myoepithelial and basement membrane markers was evaluated based on interobserver concordance.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e1.3 Interpretation of ER, PR, and HER2\u003c/h2\u003e\u003cp\u003eER and PR status were scored according to the 2020 ASCO/CAP guidelines [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Tumors with \u0026ge;\u0026thinsp;10% nuclear staining were considered positive; 1%\u0026ndash;\u0026lt;10% was designated low-positive, and \u0026lt;\u0026thinsp;1% was considered negative. For all positive cases, both the percentage and staining intensity were recorded.\u003c/p\u003e\u003cp\u003eHER2 IHC was interpreted according to the 2023 ASCO/CAP guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. IHC 0 was defined as no staining or \u0026le;\u0026thinsp;10% of tumor cells with incomplete or faint membrane staining; IHC 1\u0026thinsp;+\u0026thinsp;as \u0026gt;\u0026thinsp;10% of tumor cells with incomplete and faint membrane staining; IHC 2\u0026thinsp;+\u0026thinsp;as \u0026gt;\u0026thinsp;10% of tumor cells with weak to moderate, complete circumferential membrane staining, or \u0026le;\u0026thinsp;10% with strong complete staining; and IHC 3\u0026thinsp;+\u0026thinsp;as \u0026gt;\u0026thinsp;10% of tumor cells with strong, complete, and uniform circumferential staining. Equivocal cases (IHC 2+) were further evaluated by HER2 fluorescence in situ hybridization (FISH), and amplification was determined according to the 2023 ASCO/CAP criteria.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Clinical Characteristics\u003c/h2\u003e\u003cp\u003eAll eleven patients with DCIS-like invasive carcinoma were women, aged 43\u0026ndash;75 years (mean, 56 years). Nine tumors occurred in the left breast and two in the right. Imaging (ultrasound or mammography) revealed hypoechoic or mixed-echo nodules with either circumscribed or irregular margins. By BI-RADS classification, four cases were category 3 and seven were category 4. Maximum tumor diameter ranged from 1.5 to 5.0 cm. All lesions presented as solitary solid nodules without fibrous capsules (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinicopathological characteristics of 11 cases of DCIS-like invasive carcinoma.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLocation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTumor size\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBI-RADS (Ultrasound/Mammography)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSurgical procedure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLymph nodes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePrognosis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5x1.0x1.0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMRM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEndocrine therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e24 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.0x4.0x1.0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBreast-Conserving Surgery with SLNB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEndocrine therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e24 months, no recurrence and metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eright\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5x1.2x1.0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSimple Mastectomy with ALND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHER2-Targeted therapy plus Endocrine Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e16 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u0026times;2.0\u0026times;1.5cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBreast-Conserving Surgery with SLNB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEndocrine therapy plus radiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u0026times;1.5\u0026times;1.0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSimple Mastectomy with ALND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eChemotherapy and HER2-Targeted Therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.5\u0026times;4.0\u0026times;2.0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBreast-Conserving Surgery with SLNB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eChemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.5\u0026times;4.0\u0026times;3.2cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMRM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3/25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eChemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.7\u0026times;2.2\u0026times;1.5cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBreast-Conserving Surgery with ALND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4/24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEndocrine therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eright\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u0026times;2.0\u0026times;1.5cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBreast-Conserving Surgery with ALND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEndocrine therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.0\u0026times;3.0\u0026times;1.5cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBreast-Conserving Surgery with SLNB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEndocrine therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2 months, no recurrence or metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eleft\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5\u0026times;1.5\u0026times;1.3cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMRM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eChemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e51months,cervical lymph node metastasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eALND:Axillary Lymph Node Dissection;MRM:Modified Radical Mastectomy ;\u003cb\u003eSLNB:Sentinel Lymph Node Biopsy\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Histological features\u003c/h2\u003e\u003cp\u003eMicroscopically, tumors exhibited expansile, DCIS-like infiltration with scant stroma, smooth contours, and sharp demarcation from adjacent tissue. Peritumoral retraction spaces were occasionally present. Growth patterns included cribriform (6/11, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), papillary (3/11, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), solid (4/11, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC), comedo (5/11, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD),and Micropapillary(1/11, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE) often coexisting within the same tumor. Prominent lymphocytic infiltration was observed in comedo-type lesions (Case 5). eight cases (Cases 3, 4, 6, 7, 8, 9,10,11) contained both DCIS-like invasive carcinoma and invasive carcinoma of no special type (IBC-NST) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF), graded II or III. Conventional DCIS was also present in Cases 3, 4,9,10 and 11. In four cases (Cases 3, 7, 8 and 9), axillary lymph node metastases displayed DCIS-like cribriform structures with smooth contours, closely resembling the primary tumor (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and B). One case presented with vascular tumor thrombus resembling DCIS(Case 8, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC).A patient presented with cervical lymph node metastasis 51 months after surgery, in which a comedo-type growth pattern was observed in the metastatic lesion (Case 11, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Regarding nuclear grade of DCIS-like Growth Pattern, two tumors were low grade, two were low-to-intermediate, two was intermediate grade and five were high grade (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA: Cribriform growth pattern (Case 4, H\u0026amp;E, \u0026times;100);B:Papillary growth pattern (Case 4, H\u0026amp;E, \u0026times;100) ;C: Solid growth pattern (Case 3, H\u0026amp;E, \u0026times;100) ;D: Comedo-type growth pattern (Case 5, H\u0026amp;E, \u0026times;100) ;E: Micropapillary growth pattern (Case 9, H\u0026amp;E, \u0026times;100);F: DCIS-like invasive carcinoma coexisting with invasive carcinoma of no special type (Case 4, H\u0026amp;E, \u0026times;40) ;\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA: A loose cribriform pattern in anxillary lymph node metastases (Case 9, H\u0026amp;E, \u0026times;200);B: A dense cribriform pattern in axillary lymph node metastases (Case 3, H\u0026amp;E, \u0026times; 200); C: Tumor emboli with a DCIS-like pattern were identified within vascular spaces (Case 8, H\u0026amp;E, \u0026times;200);D:Comedo pattern in cervical lymph node metastases (Case 11, H\u0026amp;E, \u0026times;200)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHistopathological and Immunophenotypic Features of 11 Cases of DCIS-like Invasive Carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDCIS-like Growth Pattern\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade of IBC-NST\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDCIS-like Nuclear Grade\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eER/PR/Her2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHer2 FISH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKi67 Index\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMolecular Subtype\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eOriginal Pathological Diagnosis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePapillary/Cribriform\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLow grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e90% strongly positive/90% strongly positive/(2+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eencapsulated papillary carcinoma with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePapillary/Cribriform\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLow grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e70%moderate-to-strongly positive/60%moderate-to-strongly positive/(2+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eencapsulated papillary carcinoma with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid/Cribriform\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e90%strongly positive+/70%strongly positive+/(3+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNot amplified\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e50%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalB(Her2 positive)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePapillary/Cribriform\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLow- to intermediate-grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e80%strongly positive/80%strongly positive/(2+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eComedo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNegative/Negative/(3+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNot amplified\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e90%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHer2 -overexpressing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid/Comedo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-/-/(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e80%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTriple-negative type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid/Comedo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-/-/(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e90%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTriple-negative type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCribriform\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIntermediate-grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e90%strongly positive/20%strongly positive/(1+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e50%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCribriform/micropapillary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLow- to intermediate-grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e90%strongly positive/90%strongly positive/(1+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid/Comedo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIntermediate-grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e90%moderately positive/90%moderately positive/(1+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLuminalA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eComedo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIII grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh grade\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-/-/(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e90%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTriple-negative type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eIBC-NST with DCIS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eIBC-NST\u0026thinsp;=\u0026thinsp;invasive carcinoma of no special type\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Immunohistochemical findings\u003c/h2\u003e\u003cp\u003eAll tumors (11/11) lacked expression of myoepithelial markers (CK5/6, p63, CK14, SMA, Calponin), and Collagen IV confirmed loss of basement membrane (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA\u0026ndash;F, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA\u0026ndash;F). By contrast, DCIS components in Cases 3,4,9,10 and 11 showed intact myoepithelial marker expression and preserved basement membrane (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA\u0026ndash;F).\u003c/p\u003e\u003cp\u003eSeven tumors were ER-positive (70\u0026ndash;90%) and seven were PR-positive (60\u0026ndash;90%). HER2 status was 0 in three cases, 1\u0026thinsp;+\u0026thinsp;in three cases, 2\u0026thinsp;+\u0026thinsp;in three cases, and 3\u0026thinsp;+\u0026thinsp;in two cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA\u0026ndash;F, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). All HER2 2\u0026thinsp;+\u0026thinsp;tumors were non-amplified by FISH. None expressed neuroendocrine markers (Syn, CgA, CD56). Ki-67 index ranged from 5% to 90%. In Cases 3, 4, 6, 7, 9,10 and 11, IBC-NST components exhibited the same ER/PR/HER2 profiles as the DCIS-like invasive component.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA:CK5/6 demonstrating loss of myoepithelial cells ;B: CK14 demonstrating loss of myoepithelial cells;C: p63 demonstrating loss of myoepithelial cells;D: Calponin demonstrating loss of myoepithelial cells ;E:SMA demonstrating loss of myoepithelial cells;F: Collagen IV showing absent basement membrane\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA: CK5/6 demonstrating loss of myoepithelial cells;B:CK14 demonstrating loss of myoepithelial cells;C:p63 demonstrating loss of myoepithelial cells; D:Calponin demonstrating loss of myoepithelial cells;E:SMA demonstrating loss of myoepithelial cells; F: Collagen IV showing absent basement membrane\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA:CK5/6 demonstrating intact myoepithelial layer(Case3); B: CK14 demonstrating intact myoepithelial layer(Case3); C: p63 demonstrating intact myoepithelial layer(Case3); D: Calponin cytoplasmic staining forming intraluminal protrusions(Case3); E:SMA cytoplasmic staining forming intraluminal protrusions(Case3); F:Collagen IV demonstrating continuous basement membrane(Case3)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA: ER 90% strongly positive;B:PR 90% strongly positive; C: HER2 (2+); D:ER negative; E: PR negative; F:HER2 (3+)\u003c/p\u003e\u003cp\u003e(A-C: Case 4; D-F: Case 5; IHC, \u0026times;100)\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Inter-Observer Concordance Analysis of Myoepithelial Markers and Collagen IV\u003c/h2\u003e\u003cp\u003eComparative analysis of several myoepithelial markers revealed that SMA and Calponin staining exhibited cytoplasmic localization in ductal carcinoma in situ (DCIS), forming intraluminal protrusions, with positive cells positioned internal to the basement membrane. However, frequent cross-reactivity with stromal myofibroblasts and vascular pericytes introduced significant diagnostic interference. Collagen IV staining demonstrated poor reliability due to background non-specific staining and positivity in vascular basement membranes. In contrast, CK5/6, CK14, and p63 exhibited clean background staining with minimal non-specific reactivity, allowing for consistent and reliable interpretation (Figs.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eA-D).\u003c/p\u003e\u003cp\u003eTwelve pathologists independently evaluated myoepithelial markers (CK5/6, CK14, p63, SMA, Calponin) and basement membrane marker Collagen IV in 11 cases of in situ-like invasive carcinoma. CK5/6 and CK14 demonstrated perfect diagnostic performance (false-positive rate\u0026thinsp;=\u0026thinsp;0%, κ\u0026thinsp;=\u0026thinsp;1.00), whereas Collagen IV showed poor reliability (false-positive rate\u0026thinsp;=\u0026thinsp;38.6%, κ\u0026thinsp;=\u0026thinsp;0.23) and should be used cautiously with supplementary markers. Pathologists' interpretations, detailed performance metrics, and sources of discordance are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA: Calponin staining in in situ-like invasive carcinoma shows loss of myoepithelial cells. Tumor-surrounding stromal fibroblasts and pericytes are positive;B: SMA staining in in situ-like invasive carcinoma shows loss of myoepithelial cells. Tumor-surrounding stromal fibroblasts and pericytes are positive;C: Calponin staining in ductal carcinoma in situ reveals intraluminal protrusions due to cytoplasmic staining;D: SMA staining in ductal carcinoma in situ reveals intraluminal protrusions due to cytoplasmic staining.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eInterobserver Concordance in Myoepithelial/Basement Membrane Marker Interpretation for DCIS-like Invasive Carcinoma Among 12 Pathologists (11 Cases)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCase\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e\u003cp\u003eImmunohistochemical markers (Number of pathologists interpreting loss of expression / Total pathologists)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCK5/6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCK14\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP63\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSMA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCalponin\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCollagen IV\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8/12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDiagnostic Performance of Myoepithelial/Basement Membrane Markers in DCIS-like Invasive Carcinoma (n\u0026thinsp;=\u0026thinsp;132 evaluations;11 cases \u0026times; 12 pathologists)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaker\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFalse Positive Rate(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSpecificity(%)\u003c/p\u003e\u003cp\u003e(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eKappa vs,Gold Standard(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAgreement Level\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMajor Interpretive Discrepancies\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK5/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(0.0-2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e100.0(97.2\u0026ndash;100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0(1.00\u0026ndash;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAlmost perfect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCK14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(0.0-2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e100.0(97.2\u0026ndash;100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0(1.00\u0026ndash;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAlmost perfect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5(0.2\u0026ndash;5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e98.5(94.6\u0026ndash;99.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.91(0.82-1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSubstantial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eWeak nuclear staining in some luminal epithelial cells\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSMA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.9(9.9\u0026ndash;23.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e84.1(76.2\u0026ndash;90.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.68(0.56\u0026ndash;0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eInterference from pericytes and myofibroblasts\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalponin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.2(11.8\u0026ndash;26.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e81.8(73.6\u0026ndash;88.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.64(0.52\u0026ndash;0.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eInterference from pericytes and myofibroblasts\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCollagen IV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.6%(30.2\u0026ndash;47.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e61.4(52.3\u0026ndash;69.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.23(0.10\u0026ndash;0.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePoor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNon-specific staining, interference from vascular basement membranes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eNotes:\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eKappa grading based on Landis \u0026amp; Koch criteria\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Correlation Between Molecular Subtypes and Growth Patterns\u003c/h2\u003e\u003cp\u003eFour cases (n\u0026thinsp;=\u0026thinsp;4/11) with predominantly cribriform/papillary or solid/comedo growth patterns were Luminal A type(Case1, 2, 4 and 10). Three cases (n\u0026thinsp;=\u0026thinsp;3/11) were of the Luminal B subtype, including one with a solid/cribriform growth pattern (HER2-overexpressing, Case 3), one with a cribriform growth pattern (Case 8), and one with a cribriform/micropapillary growth pattern(Case 9).One case (n\u0026thinsp;=\u0026thinsp;1/11) with predominantly comedo-type growth was HER2-overexpressing(Case 5). Three cases (n\u0026thinsp;=\u0026thinsp;3/11) showing predominantly solid/comedo-type growth were triple-negative(Case6,7 and 11). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e2.6 Pathological Diagnostic Concordance\u003c/h2\u003e\u003cp\u003eTwo pure DCIS-like invasive carcinoma (Cases 1 and 2) with papillary/cribriform patterns were initially misdiagnosed as encapsulated papillary carcinoma with concurrent DCIS. Five cases (5/11, Case 3,4,9,10 and 11), which coexisted with NST and DCIS, were initially misinterpreted as DCIS due to their DCIS-like growth pattern. One case (1/11, Case 5) of pure comedo-type invasive carcinoma was correctly diagnosed as IBC-NST on routine immunohistochemistry due to the absence of myoepithelial cells. Three cases (3/11, Case 6, 7 and 8) with cribriform, solid or comedo patterns, accompanied by IBC-NST, were diagnosed as IBC-NST, with the DCIS-like invasive component being overlooked. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e2.7 Treatment and Outcomes\u003c/h2\u003e\u003cp\u003eAmong the eleven patients, modified radical mastectomy(MRM) was performed in Cases 1/7/11, breast-conserving surgery with sentinel lymph node biopsy (SLNB) in Cases 2/4/6/10, breast-conserving Surgery with axillary lymph node dissection (ALND) in Cases 8 and 9, and simple mastectomy with ALND in Cases 3 and 5. Axillary lymph node metastases were identified in Cases 3/7/8/9. Adjuvant therapy included endocrine therapy (Cases 1, 2,8,9 and 10), anti-HER2\u0026thinsp;+\u0026thinsp;endocrine therapy (Case 3), endocrine therapy\u0026thinsp;+\u0026thinsp;radiotherapy (Case 4), chemotherapy\u0026thinsp;+\u0026thinsp;anti-HER2 (Case 5), and chemotherapy (Cases 6, 7,11). After a mean follow-up of 13 months (range 2\u0026ndash;51 months), 10 patients remained disease-free and maintained good performance status, one patient presented with cervical lymph node metastasis 51 months after surgery, in which a comedo-type growth pattern was observed in the metastatic lesion (Case11). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study highlights the clinicopathological spectrum of breast invasive carcinoma with a DCIS-like growth pattern, an underrecognized entity that poses major diagnostic challenges. Importantly, we report axillary and cercical lymph node metastases retaining DCIS-like morphology, providing direct evidence that this pattern represents an invasive carcinoma rather than an in situ lesion.\u003c/p\u003e\u003cp\u003eExpansile invasion, though rarely addressed in the breast literature, can mimic DCIS due to its rounded nests, papillary, cribriform, or comedo-type structures with smooth contours and minimal stromal reaction. These features often lead to misclassification as DCIS, solid papillary carcinoma, or encapsulated papillary carcinoma. In our series, two cases were initially diagnosed as encapsulated papillary carcinoma with DCIS, DCIS-like invasive carcinoma was misclassified as DCIS in cases of IBC-NST with DCIS, while in other cases of IBC-NST the presence of DCIS-like invasive carcinoma was overlooked. Careful recognition of the absence of myoepithelial cells is essential to avoid misdiagnosis.\u003c/p\u003e\u003cp\u003eEarlier reports have described similar tumors mimicking comedo-type or micropapillary DCIS [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Zhang et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] emphasized the diagnostic value of multiple myoepithelial markers, while Wynveen et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] demonstrated that collagen IV positivity does not preclude invasion, as re-formation of basement membrane may occur after tumor penetration. Our findings support these observations and further demonstrate that diagnostic accuracy is maximized by using CK5/6 and CK14, which achieved perfect concordance among pathologists in this study.\u003c/p\u003e\u003cp\u003eIn contrast to previous studies suggesting enrichment for ER-negative phenotypes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], our cohort displayed molecular heterogeneity: Luminal A (n\u0026thinsp;=\u0026thinsp;4), Luminal B (n\u0026thinsp;=\u0026thinsp;3), HER2 overexpression (n\u0026thinsp;=\u0026thinsp;1), and triple-negative (n\u0026thinsp;=\u0026thinsp;3). Nuclear grades ranged from low to high, and comedo-type tumors were often associated with lymphocytic infiltration, suggesting that the tumor microenvironment may influence invasiveness.\u003c/p\u003e\u003cp\u003eDCIS-like invasive carcinoma must be carefully distinguished from several morphologically overlapping entities. Conventional DCIS typically retains a continuous layer of myoepithelial cells, which can be confirmed using markers such as CK5/6, CK14 and p63. In contrast, DCIS-like invasive carcinomas lack myoepithelial cells and may exhibit subtle stromal reaction, necessitating immunohistochemical confirmation across multiple markers.Encapsulated papillary carcinoma (EPC) often presents as a well-circumscribed lesion with absent peripheral myoepithelial cells but typically displays low-grade cytology and rarely metastasizes, unlike the cases presented in our study. Solid papillary carcinoma (SPC) may also be mistaken for DCIS-like invasion but frequently expresses neuroendocrine markers (e.g., synaptophysin, chromogranin) and contains delicate fibrovascular cores. Integration of morphologic assessment with immunohistochemical profiling is essential to avoid diagnostic errors and ensure appropriate clinical management.\u003c/p\u003e\u003cp\u003eThe presence of DCIS-like morphology in lymph node metastases, both in our series and in prior reports [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], underscores the invasive nature of these tumors despite their deceptively in situ-like appearance. Misinterpretation may lead to inappropriate treatment strategies. For equivocal DCIS cases, immunohistochemical confirmation of absent myoepithelial markers should be mandatory. Awareness of this entity and its key differential diagnoses\u0026mdash;including DCIS, EPC, and SPC\u0026mdash;is essential, and accurate classification requires a panel-based approach combining myoepithelial and neuroendocrine markers with morphological features.\u003c/p\u003e\u003cp\u003eThis study is limited by its small sample size, lack of genomic profiling, and short follow-up period. Larger multi-center studies integrating molecular and spatial-omics analyses are warranted to further define the biology of DCIS-like invasive carcinoma and its optimal management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDCIS \u0026nbsp; \u0026nbsp; \u0026nbsp; Ductal carcinoma in situ\u003c/p\u003e\n\u003cp\u003eIBC-NST \u0026nbsp; \u0026nbsp;Invasive breast carcinoma of no special type\u003c/p\u003e\n\u003cp\u003eSPC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Solid papillary carcinoma\u003c/p\u003e\n\u003cp\u003eEPC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Encapsulated papillary carcinoma\u003c/p\u003e\n\u003cp\u003eER \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Estrogen receptor\u003c/p\u003e\n\u003cp\u003ePR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Progesterone receptor\u003c/p\u003e\n\u003cp\u003eHER2 \u0026nbsp; \u0026nbsp; \u0026nbsp;Human Epidermal growth factor Receptor 2\u003c/p\u003e\n\u003cp\u003eIHC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;World Health Organization\u003c/p\u003e\n\u003cp\u003eCgA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Chromogranin A\u003c/p\u003e\n\u003cp\u003eSyn \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Synaptophysin\u003c/p\u003e\n\u003cp\u003eFISH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Fluorescence in situ hybridization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the study participants for making this study possible.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eXiaoyan Xu was responsible for manuscript writing, figure preparation, and data analysis. Yaozhong Zhang participated in manuscript revision. Huijuan Fang and Chuan Li conducted case collection. Xianwei Xu performed the immunohistochemical staining. Huang Jiang and Liu Yang contributed to the study design and manuscript revision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Zhengzhou City Technological Innovation Progect(2025YLZDJH311)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are included in the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures carried out in studies involving human participants complied with the ethical standards of the Research Committee of Zhengzhou People\u0026rsquo;s Hospital and the 1964 Declaration of Helsinki and subsequent amendments or similar ethical standards. The study was approved by the Bioethics Committee of Zhengzhou People\u0026rsquo;s Hospital(2025-KY-009901). All subjects gave informed consent to participate in the study. All methods were performed in accordance with relevant guidelines and regulations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCowen PN, Bates C. The significance of intraduct appearances in breast cancer. Clin Oncol. 1984;10(1):67\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSalisbury T, Rendi M, Bhalli R, et al. DCIS-like invasive carcinoma of the breast with tumour-associated microvasculature mimicking myoepithelium: a diagnostic pitfall. Histopathology. 2025;87(2):246\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJi J, Shi M, Duan F, et al. A case of invasive ductal carcinoma with in situ pattern of the breast. Chin Med Case Rep. 2023;5(1):e00232.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMohan N, Black JO, Schwartz MR, Zhai QJ. Invasive ductal carcinoma with in situ pattern: how to avoid this diagnostic pitfall? Am J Transl Res. 2016;8(8):3337\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAllison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38(12):1346\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-CAP guideline update. J Clin Oncol. 2023;41(22):3867\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePervez S, Khan H. Infiltrating ductal carcinoma of the breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type): a case series. J Med Case Rep. 2007;1:83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTijani S, Sharma K, Yuen H, Shaaban A. Metastatic ductal carcinoma in situ-like lobular carcinoma in a lymph node: a case report and review of the literature. Int J Surg Pathol. 2020;28(4):436\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang X, Ding H. Morphological changes of expansile invasion in mammary tumors and their significance in pathological diagnosis. Zhonghua Bing Li Xue Za Zhi. 2014;43(5):291\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWynveen CA, Nehhozina T, Akram M, et al. Intracystic papillary carcinoma of the breast: an in situ or invasive tumor? Results of immunohistochemical analysis and clinical follow-up. Am J Surg Pathol. 2011;35(1):1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarsky SH, Doberneck SA, Sternlicht MD, Grossman DA, Love SM. Revertant DCIS in human axillary breast carcinoma metastases. J Pathol. 1997;183(2):188\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCserni G. Revertant mammary solid papillary carcinoma in lymph node metastasis. Pathol Oncol Res. 2002;8(1):74\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoyne J. Metastatic mammary carcinoma with DCIS-like morphology: a report of two cases. Int J Surg Pathol. 2012;20:485\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKordek R. Ductal carcinoma in situ-like structures in metastatic breast carcinoma. Pathol Res Pract. 2005;200(11\u0026ndash;12):831\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu Y, Huang H, Zhang M, et al. Clinicopathological analysis of metastatic breast cancer with ductal carcinoma in situ-like growth pattern. Zhonghua Bing Li Xue Za Zhi. 2018;47(10):784\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Invasive breast carcinoma of no special type (IBC-NST), Ductal carcinoma in situ (DCIS)-like growth, diagnostic pitfall, Myoepithelial cell loss","lastPublishedDoi":"10.21203/rs.3.rs-8084081/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8084081/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDuctal carcinoma in situ(DCIS)-like invasive carcinoma is a rare variant of expansile invasive breast cancer that is frequently misdiagnosed as ductal carcinoma in situ. However, some patients develop lymph node metastases exhibiting DCIS-like features, and there is limited literature documenting its clinicopathological characteristics.To characterize the clinicopathological features, immunophenotype, and diagnostic pitfalls of breast invasive carcinoma with a DCIS-like growth pattern (DCIS-like invasive carcinoma), a retrospective review of 319 breast carcinomas (January 2021\u0026ndash;September 2025) identified 11 cases of DCIS-like invasive carcinoma. Clinical, histopathological, and immunophenotypic features were evaluated, and interobserver concordance for myoepithelial and basement membrane markers was assessed by 12 pathologists. Three tumors represented pure DCIS-like invasive carcinoma, and eight were admixed with invasive carcinoma of no special type (IBC-NST). Growth patterns included cribriform (6/11), papillary (3/11), solid (4/11), and comedo (5/11) and micropapillary(1/11). All tumors lacked myoepithelial marker expression (CK5/6, p63, CK14, SMA, Calponin), with Collagen IV confirming basement membrane loss; CK5/6 and CK14 showed perfect diagnostic reliability (κ\u0026thinsp;=\u0026thinsp;1.00). Four patients developed axillary lymph node metastases in which the metastatic foci paradoxically retained DCIS-like morphology, directly confirming their invasive nature.Hormone receptor positivity was observed in 7/11 tumors, HER2 overexpression in 2/11, and the Ki-67 index ranged from 5\u0026ndash;90%. With a mean follow-up of 13 months (range, 2\u0026ndash;51 months), no local recurrence or distant metastasis was documented in 10 patients, DCIS-like structure was identified in cervical lymph node metastasis in one patient at 51 months postoperatively. DCIS-like invasive carcinoma is a rare and underrecognized entity that closely mimics DCIS and poses significant diagnostic challenges. The presence of lymph node metastases with DCIS-like morphology underscores its invasive potential. Accurate recognition requires careful morphological assessment in combination with multiple myoepithelial markers to avoid misdiagnosis and inappropriate clinical management.\u003c/p\u003e","manuscriptTitle":"Invasive Breast Carcinoma with a DCIS-like Growth Pattern: Clinicopathological Features and Diagnostic Pitfalls","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-15 10:59:29","doi":"10.21203/rs.3.rs-8084081/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f49cd8c5-6a85-469e-a656-c60015d10f63","owner":[],"postedDate":"December 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-04T04:09:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-15 10:59:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8084081","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8084081","identity":"rs-8084081","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}